Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the world, causing serious complications on women's reproductive health including ectopic pregnancy, pelvic inflammatory disease and infertility. C. trachomatis also causes infection of the eye resulting in inflammation and in some cases blindness. The objectives of this project are to define the epidemiology, risk factors, transmission kinetics, and pathogenesis of C. trachomatis infections in different population settings, including populations in resource constrained countries. We have used the Internet site www.iwantthekit.org since 2004 to offer sampling in Maryland and other areas in the U.S. for chlamydia screening in over 7,000 women and 3800 men using self-obtained vaginal swabs, penile-meatal swabs and rectal samples. Samples were also tested for gonorrhea and trichomonas. Prevalence of chlamydia for women overall was 6.3% and 10.3% in young women age 15-19 yr. Both young age and Black race were statistically associated with chlamydia positivity. For men, the overall chlamydia prevalence was 6.2%. Acceptance for self-collecting penile and rectal swabs has been very high. Rectal chlamydia and gonorrhea prevalence for males was 2.7% and 2.7%, respectively. Rectal chlamydia and gonorrhea prevalence in wome was 6.4% and 1.1%, respectively. To study the capability for performing a point-of-care self-test for trichomonas at home, we recently enrolled 102 women who performed the mailed test successfully at home. The test demonstrated high accuracy and high acceptability and will be added to our surveys. Oral treatment of chlamydia with 100 mg of doxycycline twice daily for 7 days or with a single 1-g dose of azithromycin has been recommended since 1996. A meta-analysis of 23 randomized trials indicated that the efficacy of doxycycline was 3 percentage points higher than that of azithromycin for the treatment of urogenital chlamydia and 7 percentage points higher than that of azithromycin for the treatment of symptomatic males. In a randomized trial, directly observed treatment with doxycycline had a 100% cure rate, as compared with a 97% cure rate for azithromycin treatment. The reasons for the lower efficacy of azithromycin remain unclear. Drug resistance of chlamydia has not been definitively established. Some patients may not have sustained mucosal levels of azithromycin that are sufficient to eradicate chlamydia, and the infection may therefore be driven to a persistent viable state. Azithromycin may be more efficacious for the treatment of upper reproductive tract infection. With the above caveats in mind, it seems reasonable to recommend doxycycline over azithromycin as the preferred regimen for chlamydia treatment. However, because of low adherence with 7 days of doxycycline in some studies and the finding of very high efficacy (97% and 100%) for both treatments, we recommend that either drug be used in the treatment of persons with chlamydia infection. Trachoma due to C. trachomatis infection is the most common cause of infectious blindness in the world. The WHO has recommended that three rounds of mass drug administration (MDA) with antibiotics be offered to control the disease in districts where the prevalence of follicular trachoma (TF) is >10% in children aged 1-9 years, with treatment coverage of at least 80%. We have conducted both surgical and antibiotic treatment intervention studies in Gambia, Niger, and Tanzania in efforts to control trachoma. However, the source of infection following mass treatment is often unknown. If migrants into a village undergoing MDA are shown to impede progress towards elimination, then a local strategy that addresses treatment of new families and a nationwide strategy that addresses migration will be needed. The purpose of this study was to quantify the effect of migrants on the prevalence of infection and clinical trachoma in communities. In four communities in Kongwa, Tanzania, all children were enrolled in a longitudinal study of infection and trachoma. New children were identified at census updates as having not been in the community at the previous census. Within communities, neighborhoods were defined as spatially close groups of households. Children who were migrants were more likely to be infected and to have trachoma than children who were resident in the community, which was significant by the time of the survey following the third year of MDA (odds ratio, OR, 2.49, 95% confidence interval, CI, 1.036.05). The neighborhoods where newcomers resided were more likely to have infection a year later than neighborhoods with no migrants, which was most pronounced following the third year of MDA (OR 2.86, 95% CI 1.077.65). In summary, migrants to communities may be an important source of re-emergent infection, especially as MDA lowers infection among residents. Highly migrant populations may need a special surveillance and treatment program to avoid slowing progress in communities under MDA. Recent work on a test for antibodies to C. trachomatis antigens suggests serology is a promising tool that indicates cumulative risk of exposure to C. trachomatis. If serology can be used in the youngest age groups to monitor evidence of exposure since the cessation of mass antibiotic provision, it may prove to be a useful tool for confirming interruption of transmission. In a trachoma-endemic district in Tanzania that stopped its program four years ago, we undertook a surveillance survey, adding to the assessment of TF a lab test for C. trachomatis infection, and a dried blood spot which was processed for antibodies to C. trachomatis antigen pgp3; antibody status may indicate cumulative past exposure to infection. The prevalence of TF was 0.4%, below the 5% cut-off indicating that trachoma elimination had been achieved with no re-emergence. The antibody positivity overall was low, 7.5%, and increased with age from 5.2% in 13 year olds, to 9.3% in 79 year olds (p = 0.015). In 16 of the 30 hamlets, no children aged 13 years old had antibodies to pgp3. The antibody status of the 13 year olds indicated low cumulative exposure to infection during the surveillance period. In summary, four years post -program, there is no evidence for re-emergence of trachoma using any indicator sufficient to indicate re-emergence.